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Glucocorticoids attenuate septic acute kidney injury

Author:
Choi, Hye Min, Jo, Sang-Kyung, Kim, Sung Hwan, Lee, Jae Won, Cho, Eunjung, Hyun, Young Youl, Cha, Jin Joo, Kang, Young Sun, Cha, Dae Ryong, Cho, Won Yong, Kim, Hyoung Kyu
Source:
Biochemical and biophysical research communications 2013 v.435 pp. 678-684
ISSN:
0006-291X
Subject:
animal experimentation, apoptosis, cytochrome-c oxidase, cytokines, dexamethasone, glucocorticoids, inflammation, kidneys, light microscopy, males, mice, models, mortality, necrosis, pathogenesis, pathophysiology, protective effect, proteins, septic shock, splenocytes, surgery
Abstract:
The incidence and mortality of septic acute kidney injury (AKI) remains high, whereas our understanding of pathogenesis for septic AKI is still limited. Glucocorticoids (GCs) have been clinically recommended for treatment of septic shock and also have showed favorable effect on septic AKI in several animal experiments. The aim of this study is to investigate the pathophysiology of septic AKI and the effect of GCs on septic AKI.We induced septic AKI using cecal ligation and puncture (CLP) model in 8–10wk-old male C57BL/6 mice. Saline or dexamethasone (2.5mg/kg) dissolved in saline was administered after surgery. Hemodynamic, biochemical and histological changes were examined in a time-course manner.CLP resulted in hyperdynamic warm shock with multiple organ dysfunction including AKI. Despite renal dysfunction, light microscopy showed scanty acute tubular necrosis and inflammation. Instead, CLP induced significant increase in apoptosis of the kidney and spleen cells. In addition, septic kidneys showed mitochondrial injury and alterations in Bcl2 family proteins in the renal tubular cells. Dexamethasone treatment attenuated renal dysfunction, but it was not associated with improvement of hemodynamic parameters. Dexamethasone-induced organ protective effect was associated with reduced mitochondrial injury with preserved cytochrome c oxidase and suppression of proapoptotic proteins as well as reduced cytokine release.Mitochondrial damage and subsequent apoptosis are thought to play important role in the development of septic AKI. GCs might be a useful therapeutic strategy for septic AKI by reducing mitochondrial damage and apoptosis.
Agid:
897585